Activator and Repressor All in One

Pax-6 genes are essential for eye development and encode transcription factors with two separate DNA binding domains: a paired domain (PD) and either a paired-like homeodomain (HD) or an octapeptide. The Pax gene, eyeless (ey), in Drosophila melanogaster has an HD and a PD. Punzo et al. found that the PD domain was necessary and sufficient for eye development, but that the HD domain was dispensable for eye development. Expression of a truncated form of EY lacking the HD domain was capable of rescuing an ey mutant and inducing the formation of ectopic eyes without stimulating the expression of endogenous ey or another Pax gene, twin of eyeless (toy). However, deletion of the PD domain resulted in the loss of this activity. The HD domain appears to be important for gene repressive activity of ey, because the PD-deleted form of EY was able to repress the expression of the ey target gene distal-less, whereas the HD-deleted form did not. Thus, ey can be a gene activator through the PD domain and a gene repressor through the HD domain.